BACKGROUND:Evusheld®, a combination of monoclonal antibodies Tixagevimab and Cilgavimab, was developed for pre-exposure prophylaxis (PrEP) of coronavirus disease 2019 (COVID-19) in immunocompromised patients. However, real-world long-term data on its effectiveness against SARS-CoV-2 Omicron variants remain limited. METHODS:A retrospective cohort was conducted on patients ≥18 years old who received the Evusheld from December 1, 2021, to January 31, 2023, at six Ascension hospitals in Southeast Michigan. Patients included were those with active solid tumor and hematologic malignancies or undergoing immunosuppressive treatment, including CAR-T therapy, biologic agents, or high-dose corticosteroids (≥20 mg prednisone or equivalent per day for ≥2 weeks). Data collected included patient demographics, development of COVID-19 post-Evusheld, ICU length of stay (LOS), hospital LOS, ventilation requirement and duration, and mortality within six months post-therapy. RESULTS:Among 663 patients screened, 316 were included after excluding duplicates and patients that did not receive the ordered Evusheld regimen. Among them, 204 patients received two doses of Evusheld and 112 received only one dose. In the two-dose group, 18 (8.8%) tested positive for COVID-19 within 180 days post-Evusheld, while 11 (9.8%) in the one-dose group tested positive. Notably, none of the COVID-positive patients in either group required hospitalization, mechanical ventilation, or succumbed to the disease. CONCLUSIONS:Within six months of Evusheld administration, immunocompromised patients showed no episodes of rehospitalization, mechanical ventilation, or death, and experienced low rates of severe COVID-19.

Abstract Background Evusheld® is a combination of two monoclonal antibodies, Tixagevimab and Cilgavimab. It was developed for the pre-exposure prophylaxis (PrEP) and treatment of COVID-19 illness for those who are immunocompromised. There is paucity of long-term real-world data on the use of Evusheld among the immunosuppressed patients against the SARS-CoV-2 Omicron variants. Methods A retrospective cohort chart review of patients 18 years and older who received the two dose Evusheld regimen from December 1, 2021 to January 31, 2023 at a community teaching institution was performed to evaluate the effectiveness of Evusheld as PrEP of COVID-19 patients. Evusheld as PrEP was indicated for patients with active solid tumor and hematologic malignancies or those receiving immunosuppressive treatment including CART therapy, biologic agents and high-dose corticosteroids (i.e., ≥ 20 mg prednisone or equivalent per day when administered for ≥ 2 weeks). The following data was collected: patient demographic, development of COVID19 after receiving Evusheld®, intensive care unit (ICU) length of stay (LOS), hospital LOS, ventilation requirement, duration of ventilation, and mortality among these patients within six months of receiving Evusheld therapy. Results Of the 663 patients screened, 459 were excluded primarily for duplicate patients. The mean age of the 204 included patients was 68.3 years and 97 (47.5%) were female. Eighteen (8.8%) patients had a positive COVID-19 test within 180 days of receiving Evusheld. None of the COVID positive patients were admitted to the hospital or required mechanical ventilation. All COVID positive patients survived. Conclusion Our study shows that Evusheld was effective in preventing COVID-19 among the immunocompromised patients during the six-month follow-up period. This study also showed that patients who developed COVID-19 after Evusheld did not develop severe disease or require hospitalization. Disclosures All Authors: No reported disclosures

IMPORTANCE The morbidity and mortality associated with COVID-19 remain high despite advances in standard of care therapy, and the role of anti-inflammatory agents that inhibit the interleukin 6/JAK2 pathway is still being elucidated. OBJECTIVE To evaluate the efficacy and safety of the oral JAK2/IRAK1 inhibitor pacritinib vs placebo in the treatment of adults with severe COVID-19. DESIGN, SETTING, AND PARTICIPANTS This phase 2, double-blind, placebo-controlled, randomized clinical trial enrolled hospitalized adult patients with severe COVID-19 at 21 centers across the US between June 2020 and February 2021, with approximately 1.5 months of safety follow-up per patient. Data analysis was performed from September 2021 to July 2022. INTERVENTIONS Patients were randomized 1:1 to standard of care plus pacritinib (400mg per os on day 1 followed by 200 mg twice daily on days 2-14) vs placebo, for 14 days. MAIN OUTCOMES AND MEASURES The primary end point was death or need for invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) by day 28. All-cause mortality and safety were also assessed. RESULTS A total of 200 patients were randomized to pacritinib (99 patients; 56 men [56.6%]; median [range] age, 60[19-87] years) or placebo (101 patients; 64 men [63.4%]; median [range] age 59 [28-94] years). The percentage requiring supplementary oxygen was 99.0% (98 patients) in the pacritinib group vs 98.0% (99 patients) in the placebo group. The percentage who progressed to IMV, ECMO, or death was 17.2% (17 patients) in the pacritinib group vs 22.8% (23 patients) in the placebo group (odds ratio, 0.62; 95% CI, 0.28-1.35; P =.23). Among patients with elevated interleukin 6, the rate was 17.5% (11 of 63 patients) in the pacritinib group vs 30.4% (21 of 96 patients) in the placebo group. The adverse event rate was similar for pacritinib vs placebo (78.1% [75 patients] vs 80.2% [81 patients]), with no excess in infection (14.6% [14 patients] vs 19.8% [20 patients]), bleeding (8.3% [8 patients] vs 10.9% [11 patients]), or thrombosis (8.3%[8 patients] vs 7.9%[8 patients]). Rates of grade 3 or higher adverse events were lower with pacritinib than placebo (29.2% [28 patients] vs 40.6% [41 patients]). CONCLUSIONS AND RELEVANCE The study did not meet its primary end point in patients with severe COVID-19. Subgroup analyses may indicate specific populations with hyperinflammation that could benefit from pacritinib, although further clinical trials would be needed to confirm these effects.

Key Points Question Is the oral JAK2/IRAK1 inhibitor pacritinib superior to placebo in patients hospitalized with severe COVID-19? Findings In this phase 2 randomized clinical trial of 200 patients, the rate of progression to invasive mechanical ventilation, extracorporeal membrane oxygenation, or death by day 28 was 17.2% with pacritinib vs 22.8% with placebo. Among patients with elevated interleukin 6, the rate was 17.5% vs 30.4%. Meaning Pacritinib did not demonstrate a significant benefit over placebo in patients with severe COVID-19.